HYPERSENSITIVITY AND THE DIFFERENT TYPES.pptx

Hypersensitivity reactions

1. IMMUNOLOGY By: SEKYANZI PASCAL MLS( ASCPi )CM

2. Hypersensitivity

3. Hypersensitivity (Immunological reaction) refers to undesirable immune reactions produced by the normal immune system. Hypersensitivity reactions : When an immune response results in exaggerated/uncontrolled OR in appropriate reactions harmful (inflammation, cell destruction, or tissue injury) to the host the term hypersensitivity OR allergy used. Hypersensitivity reactions: four types; based on the mechanisms (Ab mediated or cell mediated) involved and time taken (immediate or delayed) for the reaction, a particular clinical condition (disease) may involve more than one type of reaction . Hypersensitivity 3

4. Type I Type II Type III Type IV ___________________________________ Type I, II and III Antibody Mediated Type IV Cell Mediated 4 Classification of Hypersensitivity

5. Classification of Hypersensitivity 5

6. Commonly called allergy (within 15 minutes) Mediated by IgE antibodies produced by plasma cells in response to stimulation of mast cells by an antigens. The antigens that stimulate it are called allergens (House dust, Pollens, Cosmetics, Insects, Clothing and Drugs) Exposure may be ingested, inhalation, injection or direct contact. Type I hypersensitivity reactions can be systemic (e.g., systemic anaphylaxis) or localized to a specific target tissue or organ (e.g., allergic rhinitis, asthma). Type I hypersensitivity reactions can range from life-threatening anaphylactic reactions to milder manifestations associated with food allergies. Type I (Immediate) Hypersensitivity 6

7. Immunologic Activity Mast cells (tissue basophils) are the cellular receptors for IgE , which attaches to their outer surface. Their granules contain a complex of heparin, serotonin, histamine, and zinc ions . Immediate hypersensitivity is the basis of acute allergic reactions caused by molecules released by mast cells when an allergen interacts with membrane-bound IgE . The reaction is amplified and/or modified by platelets, neutrophils and eosinophils. 7

8. MECHANISM OF TYPE 1 HYPERSENSITIVITY When a person receives the allergens it get attached to the B cells . The allergens stimulate the B cells to change into plasma cells . The plasma cells make IgE antibodies . These antibodies are called reagins . The IgE antibodies produced for the first time, get attached to the surface receptors of mast cell with the help of their Fc segment.

9. Allergen cross reacting with IgE on mast cell

10. The next time the allergen enters the body, it cross-links the Fab portions of the IgE bound to the mast cell. This triggers the mast cell to degranulate , that is, release its histamine and other inflammatory mediators. The inflammatory mediators are now able to bind to receptors on target cells which leads to dilation of blood vessels, constriction of bronchioles, excessive mucus secretion, and other symptoms of allergy.  

11. Acute allergic reactions result from the release of histamine , leukotriene C4, IL-4, and IL-13 . Cross-linking of two IgE molecules is necessary to initiate release from mast cells. Anaphylactic reaction : Anaphylaxis is the response to immunologic formation and fixation between an Ag and a tissue Ab. U sually mediated by IgE antibody and occurs in 3 stages: 1 . Ag attaches to the IgE on the membrane of mast cells/ basophils. 2. Activated mast cells and basophils release various mediators . 3. The effects produce vascular changes and activation of platelets, eosinophils, neutrophils, and the coagulation cascade. 11

12. Anaphylactoid reaction: Anaphylactoid are similar to anaphylaxis and can result from immunologically inert materials that activate serum and tissue proteases and the alternative pathway of the complement system. They are not mediated by Ag–Ab interaction ; instead, offending substances act directly on the mast cells , causing direct chemical degranulation and release of mediators, or on the tissues, such as anaphylotoxins of the complement cascade (e.g., C3a, C5a). 12

13. Atopy Atopy is the term for the genetic trait to have a predisposition for localized anaphylaxis. Atopic individuals have higher levels of IgE and eosinophils. Atopic reaction: exposure of the skin, nose, or airway to common airborne allergens produces allergen-specific IgG abs, and T cells exhibit moderate proliferation and production of interferon- γ ( IFN- γ) by type 1 helper cells and cytokines produced by T2 cells (e.g., IL-4, IL-5, IL-13 ).

14. Signs and symptoms Localized reaction : occurs as an immediate response to mediators released from mast cell degranulation. C an consist of urticaria and angioedema . Is severe but rarely fatal . Skin reactions are characterized by the appearance of redness and itching at the site of the introduction of the allergen. 14

15. Generalized reaction : is produced by mediators such as cytokines and vasoactive amines (e.g., histamine) from mast cells. Histamine release leads to constriction of bronchial smooth muscle, edema of the trachea and larynx, vasodilation, increased vascular permeability, and stimulation of smooth muscle in the GI tract , which causes vomiting and diarrhea . The resulting breakdown of cutaneous vascular integrity results in urticaria and angioedema ; vasodilation causes a reduction of circulating blood volume and a progressive fall in blood pressure , leading to shock . Antihistamines have no effect on histamine release and are less effective in preventing bronchoconstriction . 15

16. MEDIATORS OF TYPE 1 Histamine Cytokines TNF- a , IL-1, IL-6. Chemoattractants for Neutrophils and Eosinophils. Enzymes tryptase, chymase, cathepsin. Changes in connective tissue matrix, tissue breakdown Leukotrienes Prostaglandins

17. Testing for Type I Hypersensitivity P atient history, physical examination , in vivo testing protocol- skin puncture test (SPT) can also be used to assist in the identification of foods that may provoke allergic reactions. Place a drop of a solution containing a possible allergen on the skin . Scratches or needle prick to allow the solution to enter the skin. If the skin develops a red, raised, itchy area, this is a positive reaction , which means that the person is allergic to that particular allergen. The procedure carries the risk of triggering a systemic reaction (e.g., anaphylactic reaction) or initiating a new sensitivity. A patch test may be used for the evaluation of contact food allergens . Skin patch testing involves taping a patch that has been soaked in the allergen solution to the skin for 24 to 72 hours. This type of testing is used to detect contact dermatitis . Total IgE and specific IgE antibodies are measured by a modification of enzyme immunoassay (ELISA). 17

18. Cytotoxic ( Abs other than IgE ) The distinction between types II and III is based on where the complex of antibody and antigen form. I n type II, the target is fixed in the tissues or on the cell surface ; in type III the target is soluble and circulating immune complexes are formed . Type II hypersensitivity involves IgG or IgM antibody-mediated IgM or IgG immunoglobulin react with cell-surface antigens to activate the complements system and produce direct damage of the cell surface. Transfusion reactions and hemolytic disease of the newborn are examples of type II hypersensitivity. Type II ( Cytotoxic ) Hypersensitivity 18

19. Three different mechanisms of type II exist: Antibody-dependent, complement-mediated cytotoxic reactions . IgM and IgG bound on cellular antigens activate complement and ultimately cytolysis, e.g., immediate transfusion reactions and immune hemolytic anemias (e.g., HDFN). Antibody-dependent, cell-mediated cytotoxicity . Depends on the initial binding of antibodies to target cell surface antigens. The antibody-coated cells are lysed by effector cells , such as natural killer (NK) cells and macrophages, expressing Fc receptors. Target cell destruction occurs when cytotoxic substances are released by the effector cells. This is the mechanism of injury in antibody-mediated glomerulonephritis . Antireceptor antibodies . Antibodies bind to receptors of hormones (autoimmune hypersensitivity against solid tissue), as in autoimmune thyroid disease or Hyperacute graft rejection. 19

20. These reactions are classified into 2 types, ISOIMMUNE REACTION AUTOIMMUNE REACTION ISOIMMUNE REACTION Reaction brought about by the antigen and antibody of two individuals belonging to the same species. 1. Transfusion reaction 2. Erythroblastosis foetalis 3. transplant rejection reaction

21. Cont.. AUTO IMMUNE REATION Reaction brought about by the interaction of antigen and antibody of the same individual. It include autoimmune hemolytic anaemia. The individuals produces antibodies against his own RBC antigens. The red cell coated with antibodies are destroyed in the spleen and liver.

22. Hemolytic disease of newborn Rh factor incompatibility IgG abs to Rh an innocuous rbc antigen Rh + baby born to Rh - mother first time fine. 2nd time can have abs to Rh from 1st pregnancy. Ab crosses placenta and baby kills its own rbcs . Treat mother with ab to Rh antigen right after birth and mother never makes its own immune response.

23. Diagnostic evaluation ABO blood grouping Rh testing Screening for irregular antibodies; identification and tittering of any antibodies Amniocentesis (prenatal) Serum bilirubin of cord or infant blood DAT of cord or infant blood Peripheral blood smear 24

24. Hypersensitivity Type III

25. Type III (Immune Complex–Mediated) Hypersensitivity Type III hypersensitivity is also known as immune complex hypersensitivity. IgG mediated The reaction may take 3 - 10 hours after exposure to the antigen. The reaction may be general ( e.g. , serum sickness) or may involve individual organs including skin ( e.g. , systemic lupus erythematosus, Arthus reaction), kidneys ( e.g. , lupus nephritis), lungs ( e.g. ,  aspergillosis ), joints ( e.g. , rheumatoid arthritis) including or other organs. Antigens causing immune complex mediated injury are: Exogenous Endogenous Type III (ICM) Hypersensitivity 26

26. Mechanism of Type III Hypersensitivity When enormous amount of soluble antigens enter the body , antibodies are produced by B cells. Antigens combines with antibody within circulation and form immune complexes Wherever in the body they deposited (blood vessel walls and tissues) They activate complement system The complement 3(C3) and 5(C3) produce active factors called anaphylotoxin and chemotoxin . Anphylotoxin triggers the mast cells to release vasoactive amines. The amines increases the tissue permeability. Polymorphonuclear cells are attracted to the site by chemotoxin Result in releases of hydrolytic enzymes, thus inflammation and tissue injury Type III (ICM) Hypersensitivity 27

27. The mechanism of type III (immune-complex mediated) hypersensitivity-overview Antigens combine with antibodies to form antigen-antibody complexes. Antigen Antibody (IgG) Antigen-antibody complex Phagocytes remove most of the complexes, but some lodge in the walls of blood vessels. There the complexes activate complement. Inactive complement Active complement Antigen-antibody complexes and activated complement attract and activate neutrophils, which release inflammatory chemicals. Neutrophil Inflammatory chemicals Inflammatory chemicals damage underlying blood vessel wall.

28. Type III (ICM) Hypersensitivity 30 Hypersensitivity Type III Reactions Systemic Reactions Local Reactions Arthus Reaction: It is named for Dr. Arthus . Inflammation caused by the deposition of immune complexes at a localized site. Clinical Manifestation is : Hypersensitivity Pneumonitis Serum Sickness: Systemic inflammatory response to deposited immune complexes at many areas of body. Few days to 2 weeks after injection of foreign serum or drug it results in : Fever, Urticaria , Artheralgia , Eosinophila , Spleenomegally , and Lymph adenopathy

29. Immune Complex Diseases

30. Immune Complex Diseases : Hypersensitivity Pneumonitis Glomerulonephritis Rheumatoid Arthritis Systemic Lupus Erythematosus 32 Type III (ICM) Hypersensitivity

31. Testing for Type III Hypersensitivity Specific autoimmune disorders assay some use latex agglutination, nephelometry , and chemiluminescence techniques . Fluorescent staining of tissue biopsy specimens to observe the deposition of immune complexes in tissues. Q uantitation of complement (C3 and C4). 33

32. Hypersensitivity Type IV

33. Type IV (Delayed or Cell-Mediated) Hypersensitivity Delayed hypersensitivity is a function of T Lymphocytes, not antibody . M oderated by the link between T lymphocytes and phagocytic cells. It starts hours (or Days) after contact with the antigen and often lasts for days. It can be transferred by immunologically committed (Sensitized) T cells, not by serum. Principal pattern of immunologic response to variety of intra cellular microbiologic agents i.e.: Mycobacterium Tuberculosis Viruses Fungi Parasites Type IV (Cell Mediated) Hypersensitivity 35

34. Mechanism of Type IV Hypersensitivity Activated T Lymphocytes Release of cytokines and macrophage activation T-cell mediated cytotoxicity NB: T cells do not recognize the antigens but are immunologically active through direct cell-to-cell contact and by the production of soluble factors . 36 Type IV (Cell Mediated) Hypersensitivity

35. 37 Type IV (Cell Mediated) Hypersensitivity

36. Clinically Important Delayed Hypersensitivity Reactions

37. The tuberculin response An injection of tuberculin beneath the skin causes reaction in individual exposed to tuberculosis or tuberculosis vaccine Used to diagnose contact with antigens of M. tuberculosis No response when individual not infected or vaccinated Red, hard swelling (10+ mm) develops after 48 or 72 hours in individuals previously infected or immunized Other antigen include diphtheria toxoid, tetanus toxoid, fungal antigens (e.g., Trichophyton , histoplasmin ), and Candida albicans using a patch test . Type IV (Cell Mediated) Hypersensitivity 40

38. A positive tuberculin test

39. Allergic contact dermatitis Cell-mediated immune response Results in an intensely irritating skin rash Triggered by chemically modified skin proteins that the body regards as foreign Acellular, fluid-filled blisters develop in severe cases Can be treated with glucocorticoids Type IV (Cell Mediated) Hypersensitivity 42

40. Allergic contact dermatitis

41. Graft rejection Rejection of tissues or organs that have been transplanted Grafts perceived as foreign by a recipient undergo rejection Immune response against foreign MHC on graft cells Rejection depends on degree to which the graft is foreign to the recipient Based on the type of graft Type IV (Cell Mediated) Hypersensitivity 44

42. Types of grafts Autograft Isograft Allograft Xenograft Genetically identical sibling or clone Genetically different member of same species

43. Comparison of Different Types of hypersensitivity characteristics type-I anaphylactic type-II ( cytotoxic ) type-III (immune complex) type-IV (delayed type) antibody IgE IgG, IgM IgG, IgM None antigen exogenous cell surface soluble tissues & organs response time 15-30 minutes minutes-hours 3-8 hours 48-72 hours appearance weal & flare lysis and necrosis erythema and edema, necrosis erythema and induration histology basophils and eosinophil antibody and complement complement and neutrophils monocytes and lymphocytes transferred with antibody antibody antibody T-cells examples allergic asthma, hay fever erythroblastosis fetalis, Goodpasture's nephritis SLE, farmer's lung disease   tuberculin test, poison ivy, granuloma

44. Hypersensitivity Reactions Conclusion: 47

45. Questions 48